Action of prolactin, prolactin-releasing peptide and orexins on hypothalamic neurons of adult, early postnatally overfed rats.

OBJECTIVES: Hypothalamic neurons of rats overweight due to early postnatal overfeeding (SL) differ from those of control rats in their responses to feeding relevant hormones like leptin or insulin. The question arose whether prolactin and prolactin-releasing peptide (PrRP) express also differential action in SL rats. These peptides are described to have an effect on food intake and body weight regulation. Prolactin is co-synthesized in lateral hypothalamic neurons together with orexins that were also analyzed in this study.

METHODS: Single unit activity was extracellularly recorded in brain slices from adult control rats (CL) and from rats previously raised in small litters (SL). The action of the peptides on the firing rates was evaluated in the medial parvicellular part of the paraventricular nucleus (PaMP) and the medial arcuate nucleus (ArcM).

RESULTS: In control rats, PrRP significantly activated PaMP neurons, whereas prolactin and orexin-A induced also inhibition. In SL rats, there was a significantly different effect of orexin-B on PaMP neurons: the main effect changed from activation in controls to inhibition. ArcM neurons of both control and SL rats were mainly excited by prolactin and orexins.

CONCLUSION: Changes acquired during early development of neuronal responses to feeding relevant peptides are not a general non-specific mechanism of neurochemical plasticity, but concern specific hypothalamic nuclei and/ or hormones and neuropeptides. The increase in inhibition by orexin-B of hypothalamic paraventricular neurons could in vivo contribute to the neonatally acquired disposition towards persistingly increased food intake and reduced energy expenditure of overweight SL rats.

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